Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
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DOI:
10.1016/j.molcel.2011.12.020
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发表时间:
2012-01-13
期刊:
影响因子:
16
通讯作者:
Thompson, Craig B.
中科院分区:
文献类型:
--
作者:
Gruber, Joshua J.;Olejniczak, Scott H.;Yong, Jeongsik;La Rocca, Gaspare;Dreyfuss, Gideon;Thompson, Craig B.
Ars2 is a component of the nuclear cap-binding complex that contributes to microRNA biogenesis and is required for cellular proliferation. Here we expand on the repertoire of Ars2-dependent microRNAs and determine that Ars2 regulates a number of mRNAs, the largest defined subset of which code for histones. Histone mRNAs are unique among mammalian mRNAs because they are not normally polyadenylated, but rather cleaved following a 3′ stem loop. A significant reduction in correctly processed histone mRNAs was observed following Ars2 depletion, concurrent with an increase in polyadenylated histone transcripts. Furthermore, Ars2 physically associated with histone mRNAs and the non-coding RNA 7SK. Knockdown of 7SK led to an enhanced ratio of cleaved to polyadenylated histone transcripts, an effect dependent on Ars2. Together, the data demonstrate that Ars2 contributes to histone mRNA 3′ end formation and expression and these functional properties of Ars2 are negatively regulated by interaction with 7SK RNA.
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